Brain regeneration mechanism may help trigger remyelination

January 25, 2019

Multiple sclerosis is characterized by damage to the 'myelin sheath', a protective covering wrapped around nerve cells akin to insulation around an electrical wire. Researchers from Charité-Universitätsmedizin Berlin have discovered how the body initiates repair mechanisms that limit the extent of any damage to this sheath. The findings may provide a basis for the development of new drugs to treat MS.

Charité's research team took a closer look at the body's innate ability to heal itself, knowing that, under certain conditions, the central nervous system is capable of repairing damage to the myelin sheath. Specific molecular signals enable stem cells to differentiate into myelin repair cells (oligodendrocytes), which reside in a small stem-cell niche in the brain. Once they leave this niche, these repair cells migrate to where myelin damage has occurred in order to restore the affected nerve cells' electrical insulation.

Until now, very little had been known about the molecular signals responsible for initiating this myelin regeneration mechanism. The researchers found that the Chi3l3 protein plays a central role in the body's capacity to produce new myelin-forming oligodendrocytes. The Chi3l3 protein initiates the differentiation of neural stem cells into myelin repair cells, which restore the electrical insulation around damaged nerve cells.

Using a mouse model, the research team were able to show that a reduction in Chi3l3 levels in the brain significantly impairs the body's capacity for oligodendrocyte production, while a Chi3l3 infusion leads to an increase in the production of myelin repair cells. The same reaction was observed during an in vitro experiment using human cells.

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the researchers hope to use this knowledge to develop a new generation of drugs that can be used in the treatment of MS. As a next step, they will study in greater detail whether Chi3l3 or related proteins can be used to reduce the neurological symptoms of patients with MS.